Common nonsynonymous variants in PCSK1 confer risk of obesity.
Research output: Contribution to journal › Journal article › Research › peer-review
Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
Original language | English |
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Journal | Nature Genetics |
Volume | 40 |
Issue number | 8 |
Pages (from-to) | 943-5 |
Number of pages | 2 |
ISSN | 1061-4036 |
DOIs | |
Publication status | Published - 2008 |
Bibliographical note
Keywords: Adult; Case-Control Studies; Child; European Continental Ancestry Group; Genetic Predisposition to Disease; Humans; Obesity; Polymorphism, Single Nucleotide; Proprotein Convertase 1
ID: 8466806